1. Field of the Invention
The present invention relates generally to medical devices and methods. More particularly, the present invention relates to methods and systems for injecting liquid drugs into tissues surrounding body lumens, absorbing portions of the injected drugs as they pass out of the tissue at the luminal interface, and releasing the absorbed drugs back into the luminal tissue over time.
Coronary artery disease is the leading cause of death and morbidity in the United States and other western societies. In particular, atherosclerosis in the coronary arteries can cause myocardial infarction, commonly referred to as a heart attack, which can be immediately fatal or, even if survived, can cause damage to the heart which can incapacitate the patient.
While coronary artery bypass surgery is an effective treatment for stenosed arteries resulting from arthrosclerosis and other causes, it is a highly invasive procedure which is also expensive and which requires substantial hospital and recovery time. Percutaneous transluminal angioplasty (PTCA), commonly referred to as balloon angioplasty, is less invasive, less traumatic, and significantly less expensive than bypass surgery. Until recently, however, balloon angioplasty has not been considered to be as effective a treatment as bypass surgery. The effectiveness of balloon angioplasty, however, has improved significantly with the introduction of stenting which involves the placement of a scaffold structure within the artery which has been treated by balloon angioplasty. The stent inhibits abrupt reclosure of the artery and has some benefit in reducing subsequent restenosis resulting from hyperplasia.
Despite such improvement, patients who have undergone angioplasty procedures with subsequent stenting still suffer from a high incidence of restenosis resulting from hyperplasia. Very recently, however, experimental trials have demonstrated that the coating of stents with anti-proliferative drugs can significantly reduce the occurrence of hyperplasia, promising to make combined angioplasty and stenting a viable alternative to bypass surgery.
While holding great promise, the ability of drug-coated stents to inhibit hyperplasia is limited by the ability to bind effective amounts and concentrations of the drug onto the surface of the stent or other vascular prosthesis being used. In particular, the ability to load anti-hyperplastic drugs can be limited by the nature of the drug, the surface of the stent or other vascular prosthesis to which the drug is to be bound, or other causes.
In an effort to enhance the effectiveness of anti-hyperplastic drugs bound to stents, a common approach has been to entrap the drugs in a polymer matrix which is coated or otherwise disposed over the stent surface. While the use of such a polymer matrix may increase the amount of drug and/or provide for desired controlled release characteristics, such passive containment of the drug has a number of limitations.
As an alternative to using a polymer matrix, stents have also been provided with open reservoirs for holding drugs. Usually, the reservoirs will be covered by a porous membrane for maintaining the drug prior to use and releasing the drug in a controlled manner over time after the stent has been implanted.
Regardless of the particular approach chosen, drug-coated stents suffer from a number of shortcomings. In particular, the delivery and release of a drug from a stent will only provide drug at the luminal wall and not directly into the tissue surrounding the lumen. The amounts and concentrations of drugs carried by a stent is necessarily limited by the available surface area in the case of coated stents and the available stent volume in the case of stents having reservoirs. Moreover, delivering of the said drug at the luminal interface can be problematic since significant portions of the drug may be washed away, particularly in the case of drugs being delivered into blood vessels. Additionally, the delivery kinetics of the drug into the vascular or other luminal wall can be difficult to control and can require significant compromises in the design of the stent and the formulation of the drug being delivered.
As an alternative to stent-based luminal drug delivery, the direct injection of drugs into vascular and other luminal walls has recently been proposed. Of particular interest to the present invention, catheters carrying microneedles capable of delivering therapeutic and other agents deep into the adventitial layer surrounding blood vessel lumens have been described in co-pending application Ser. Nos. 09/961,080, filed on Sep. 20, 2001, and 09/961,079, also filed on Sep. 20, 2001, both applications having common inventorship with the present application. While the methods and apparatus described in these applications provide for highly advantageous luminal drug delivery, there are limitations associated with such injection protocols. First, injection requires the use of a catheter and can generally only be carried out once during an interventional procedure. Second, injected drugs, even those which are injected deep into the adventitia can be lost as they migrate to and through the luminal wall. Efforts to formulate injected drugs so that they have enhanced persistence in the tissue can require compromises with respect to other desirable drug characteristics.
For these reasons, it would be desirable to provide improved methods, systems, and apparatus for delivering drug to the tissues surrounding blood vessels and other body lumens. In particular, such improved methods and systems should overcome at least some of the deficiencies noted above with respect to drug delivery from stents and drug delivery via injection. More specifically, it would be desirable to combine beneficial aspects from each of the known delivery routes in order to provide for delivery of the drug into the adventitia with minimum loss of the drug in to the body lumen. At least some of these objectives will be met by the inventions described hereinbelow.
2. Description of the Background Art
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